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Title: Moxetumomab Pasudotox (Lumoxiti ) and Rituximab (Rituxan ) for Relapsed Hairy Cell Leukemia

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ClinicalTrials.gov Identifier: NCT03805932
Recruitment Status : Not yet recruiting
First Posted : January 16, 2019
Last Update Posted : April 24, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

Hairy cell leukemia (HCL) is a rare, slow-growing blood cancer in which the bone marrow makes too many of certain white blood cells. The antibody Rituximab binds to a protein in cancerous white blood cells and is often used to treat HCL. Researchers want to see if combining it with the drug Moxetumomab pasudotox (also called Lumoxiti) can fight HCL better.

Objective:

To test the safety of Moxetumomab pasudotox taken with Rituximab for people with HCL or HCL variant.

Eligibility:

People age 18 years and older with HCL or HCL variant that has not responded to standard therapy

Design:

Participants will be screened with:

Medical history

Physical exam

Blood, heart, and urine tests

Test of blood oxygen levels

Review of bone marrow. This can be from previous test results or a new sample.

Scans

Exercise test

Participants will get the study drugs in up to 8 cycles. A cycle will last about 28 days.

Both drugs will be given through a plastic tube in a vein.

In the first week of cycle 1, participants will have:

1 visit to get Rituximab for 7.5 hours

3 visits to get Lumoxiti for 30 minutes per infusion

In the first week of cycles 2 8, participants will have:

  1. visit to get Rituximab for 2 4 hours and Lumoxiti for 30 minutes
  2. visits to get Lumoxiti for 30 minutes per infusion

Participants will be asked to drink lots of water and take aspirin during the cycles. They will get drugs to minimize allergic reactions.

Participants will repeat screening tests at visits throughout the cycles and 1 follow-up visit. They may have an eye exam.

Sponsoring Institute: National Cancer Institute


Condition or disease Intervention/treatment Phase
Hairy Cell Leukemia Drug: Moxetumomab Pasudotox Biological: Rituximab Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of Moxetumomab Pasudotox (Lumoxiti) and Rituximab (Rituxan) for Relapsed Hairy Cell Leukemia
Estimated Study Start Date : April 29, 2019
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : June 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia
Drug Information available for: Rituximab

Arm Intervention/treatment
Experimental: 1
Moxetumomab Pasudotox + Rituximab
Drug: Moxetumomab Pasudotox
Moxetumomab pasudotox is administered at 30-40 ug/Kg iv over 30 min given on days 1, 3, 5 of each cycle.

Biological: Rituximab
Rituximab will be administered at 375mg/m(2) iv, 50- 400 mg/hr. On cycle 1, Rituximab is given on day -2, on subsequent cycles, Rituximab is given on day 1.




Primary Outcome Measures :
  1. Safety and Toxicity [ Time Frame: 4 weeks ]
    Response rate and duration of response



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Diagnosis of HCL or HCLv.
  • Treatment required for either 1) Absolute neutrophil count (ANC) <1/nL, 2) Hemoglobin <10g/dL, 3) Platelets<100/nL, 4) symptomatic splenomegaly, or 5) enlarging HCL mass > 2cm in short axis. Patients who have eligible blood counts within 4 weeks from the initiation of study will not be considered ineligible if subsequent blood counts prior to enrollment fluctuate and become ineligible up until the time of enrollment.
  • Patients must be Pseudomonas-immunotoxin na(SqrRoot) ve.
  • HCL or HCLv with at least 1 prior purine analog, and, for HCL patients with >2-year response, at least 1 other therapy. Age greater than or equal to 18 years as the disease under study, HCL/HCLv, has not been reported in children < age 18.
  • ECOG performance status less than or equal to2 (Karnofsky greater than or equal to 60%)
  • Patients must have adequate organ and marrow function as defined below:

    • Total bilirubin less than or equal to 1.5 mg/dL, unless consistent with Gilbert s (ratio between total and direct bilirubin > 5)
    • AST and ALT less than or equal to 3x upper limit of normal (ULN)
    • Alkaline phosphatase < 2.5 ULN
    • Serum creatinine less than or equal to 1.5 mg/dL or creatinine clearance greater than or equal to 60 mL/min by Cockcroft-Gault equation, where creatinine clearance = (140-age)(Kg weight)/(72 x Creatinine)
    • Serum albumin greater than or equal to 2 g/dL
    • Partial thromboplastin time (PTT) or Prothrombin time (PT)/International Normalized Ratio < 2.5x ULN (If on warfarin, PT/INR < 3.5x ULN; If on any other anticoagulation, Prothrombin time (PT) < 2.5x baseline)
    • Fibrinogen greater than or equal to 0.5 lower limit of normal
  • The effects of moxetumomab pasudotox and rituximab on the developing human fetus are unknown therefore participants must use effective methods of contraception as directed below.

    • Females of childbearing potential who are sexually active with a non-sterilized male partner must use a highly effective method of contraception prior to study entry and or the duration of study participation and must agree to continue using such precautions for 4 months after completion of moxetumomab pasudotox administration. Contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or those who are premenarchal or postmenopausal (defined as 12 months with no menses without an alternative medical cause). A highly effective method of contraception is defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. Not all methods of contraception are highly effective. Female subjects must use a hormonal method in addition to a barrier method alone, to minimize the chance of pregnancy. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
    • Non-sterilized males who are sexually active with a female partner of childbearing potential must use an effective method of contraception from Day 1 until 90 days after receipt of the final dose of investigational product. It is required that a female partner of a male subject also use an effective method of contraception throughout this period.
  • Ability of subject to understand and the willingness to sign a written informed consent document.
  • Patients must be willing to co-enroll in the investigator s companion protocol 10C-0066 titled Collection of Human Samples to Study Hairy Cell and other Leukemias, and to Develop Recombinant Immunotoxins for Cancer Treatment.

EXCLUSION CRITIERIA:

  • Patients who have had chemotherapy, immunotherapy or radiotherapy within 4 weeks or treatment with rituximab within last 3 months prior to initiation of treatment.
  • Patients who are receiving any other investigational agents.
  • Is pregnant or breastfeeding or expecting to conceive within the projected duration of the study, starting with the screening visit through 4 months after the last dose of trial treatment. Pregnant women are excluded from this study because moxetumomab pasudotox and rituximab are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with moxetumomab pasudotox and rituximab, breastfeeding should be discontinued if the mother is treated with moxetumomab pasudotox and rituximab.
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, uncontrolled pulmonary infection, pulmonary edema or psychiatric illness/social situations that would limit compliance with study requirements.
  • Patients with retinal or choroidal detachment.
  • Positive for Hepatitis B core antibody or surface antigen unless the patient is on Lamivudine or Entecavir and Hepatitis B Viral deoxyribonucleic acid (DNA) load is <2000 IU/mL
  • Active second malignancy requiring treatment other than minor resection of indolent cancers like basal cell and squamous skin cancers.
  • Human immunodeficiency virus (HIV)-positive patients unless taking appropriate anti-HIV medications with a CD4 count of > 200. Otherwise, there may be an increased risk of lethal infections when temporarily suppressing normal B-cells.
  • History of an allogeneic bone marrow transplant.
  • Patients with a history of both thromboembolism and known congenital hypercoagulable conditions.
  • Radioimmunotherapy within 2 years prior to enrollment in the study.
  • Patients with history of thrombotic microangiopathy or thrombotic microangiopathy /HUS.
  • Patients with corrected QT interval (Frederica) elevation > 500 msec (manually over-read by medically qualified person) based on at least two separate 12-lead ECGs.
  • Patients on high dose estrogen (defined as > 0.625 mg/day of an estrogen compound).
  • Oxygen saturation at rest < 88% measured by pulse oximetry or PaO2 less than or equal to 55 mm Hg.
  • Patients with life expectancy of less than 6 months.
  • Patients with clinical evidence of disseminated intravascular coagulation (Grade 3-4).
  • Patients with < 50% of predicted forced expiratory volume (FEV1) or < 50% of predicted diffusing capacity for carbon monoxide, corrected for hemoglobin concentration and alveolar volume (DLCO). Note: Patients with no prior history of pulmonary illness are not required to have pulmonary function testing (PFT). Forced expiratory volume will be assessed after bronchodilator therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03805932


Contacts
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Contact: Julie C Feurtado, R.N. (301) 402-5633 julie.feurtado@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Not yet recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Robert J Kreitman, M.D. National Cancer Institute (NCI)

Additional Information:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03805932     History of Changes
Other Study ID Numbers: 190042
19-C-0042
First Posted: January 16, 2019    Key Record Dates
Last Update Posted: April 24, 2019
Last Verified: January 11, 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
HCL Variant
Recombinant Immunotoxin
Monoclonal Antibody
Targeted Therapy
Biologic Therapy

Additional relevant MeSH terms:
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Leukemia
Leukemia, Hairy Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Immunotoxin HA22
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents